Reagents for enhanced detection of low volatility analytes

ABSTRACT

Volatilization reagents are disclosed for improved detection of inorganic oxidizers such as chlorates and perchlorates by mass spectrometry. Thermal desorption methods are also disclosed in which the reagent transfers a proton to the anion (i.e., chlorate, perchlorate, etc.) of an inorganic salt analyte, forming an acid (i.e., chloric acid, perchloric acid) that is more easily vaporized and, hence, more easily detected. The reagents can include acidic salts or cation-donators, more generally. The class of reagents including polymeric acids, polymeric organic acids and polymeric sulfonic acids. Hydrated reagents or other reagents that can release water can also be employed as co-reagents. Further, these reagents can be embedded in a swipe or other substrate, delivered as a liquid infused via nebulizer, or otherwise introduced to a sample to be tested.

REFERENCE TO RELATED APPLICATIONS

The present application claims priority to a provisional patentapplication having application No. 61/975,275 entitled “Reagents forEnhanced Detection of Low Volatility Analytes,” filed on Apr. 4, 2014,which is herein incorporated by reference in its entirety. Thisapplication is also a continuation-in-part of U.S. patent applicationSer. No. 13/948,423 entitled “Reagents For Oxidizer-Based ChemicalDetection” filed Jul. 23, 2013, which is herein incorporated byreference in its entirety. This application further incorporates byreference in its entirety U.S. Provisional Patent Application No.61/806,636 entitled “Novel Reagents For Oxidizer-Based Explosives ForUse With Ambient Ionization Technology” filed Mar. 29, 2013.

GOVERNMENT RIGHTS

This invention was made with U.S. government support under No.FA8721-05C-0002 awarded by the U.S. Air force. The Government hascertain rights in the invention.

BACKGROUND OF INVENTION

The technical field of this invention is spectrometry, e.g., ionmobility spectrometry and the like, and in particular to methods andreagents that can enhance the ionization of low volatility analytes.

The threats posed by concealed explosives and the intentional release oftoxic chemicals continue to drive improvements in ways to detect thesethreats as a means to protect the public. One technique used to aid inthis mission involves identification of the threat molecule by firstionizing it, and then detecting whether the threat molecule (analyte) ispresent. Ion mobility spectrometry (IMS), differential mobilityspectrometry (DMS), field asymmetric ion mobility spectrometry (FAIMS),and mass spectrometry (MS) are all methods used to identify moleculesthat first require ionization. Given the importance of these techniquesto public safety, considerable effort has been devoted to develop thebest means to collect the sample from the environment, present thesample to the instrument, and to also ionize it efficiently and, ifpossible, selectively in order to provide the greatest detectioncapability. In almost all instances, the ionization is achieved atambient-pressure using a technique called ambient-pressure ionization(API) (also sometimes called atmospheric-pressure chemical ionization).Because the ionization occurs in the gas phase through ion-moleculecollisions, it is usually essential that the analyte is first vaporizedto be present in the gas phase.

However, many of the explosive and chemical threats have low vaporpressure and exist as traces of solid particulates or thin films onsurfaces, and thus the most common way to collect the sample requires aswipe or swab substrate which provides a physical mechanism to bothcollect and preconcentrate the sample off the contaminated surface forsubsequent presentation to the ionization space of the detectioninstrument. The substrate media, or “swipe”, containing the collectedsample can be used to present the sample to the ionization instrument inone of two ways. In the first method, the swipe can be extracted using asolvent to selectivity dissolve the collected analyte into a solventliquid, which is then presented to the ionization space of theinstrument via a process called electrospray ionization. (See U.S. Pat.Nos. 8,513,596; 5,157,260; and 5,756,994, for examples of thisapproach). This requires extraction, dissolution, and injection stepsand, although effective, is not practical in field settings. Thealternative, and currently preferred, method is to heat the swipe todesorb the target chemical into the vapor phase for subsequentionization and detection.

In a typical API system, a swipe or swab substrate is positioned in athermal desorber located on the inlet side of the detection system.Thermal heating of the solid analyte particles on the swipe induces asolid-to-vapor phase transition and releases the analyte molecules as avapor, usually guided into the sensor inlet by a carrier gas, andionization occurs in the vapor phase. Properties ofcommercially-available swipe media have been optimized over the yearsfor increased efficiency of particle collection from surfaces(mechanical or electrostatic), efficient transfer and release of analyteinto the chemical sensor, thermal stability, and low chemical backgroundof the substrate. Prior art exists in the patent literature on differentembodiments of sampling swipes (e.g., US2006-0192098; EP1844189 andWO2007-066240). See also, commonly-owned U.S. patent application Ser.No. 13/832,905 filed entitled “Reagent Impregnated Swipe for ThermalDesorption Release and Chemical Detection with Ambient IonizationTechniques,” which discloses reagents that are chemically embedded inthe swipe material for interaction with the analyte.

One area where such an approach may be beneficial is for detection ofmaterials such as the sodium and potassium salts of chlorate andperchlorate, which do not have appreciable vapor pressures to allow forsensitive detection at desorption temperatures less than 250° C.Reagents that convert these compounds to more volatile compounds attemperatures less than 250° C. can thus provide one means to improveperformance of API-based detection systems and/or allow for operation atlower temperatures.

SUMMARY OF THE INVENTION

In one aspect, the use of volatilization reagents is disclosed forimproved detection of inorganic oxidizers such as but not limited tochlorates, perchlorates, permanganates, dichromates, and osmiumtetraoxides. In some embodiments, detection methods are disclosedwhereby a reagent can transfer a proton to the anion (i.e., chlorate,perchlorate, etc.) of an inorganic salt analyte, forming an acid (i.e.,chloric acid, perchloric acid) that is easier to detect by a mechanismwhereby the acidified reagent is more easily vaporized, and hence, moreeasily detected. Concurrently, the anion of the acid forms a new saltwith the cation released from the salt that was acidified. In anotheraspect of the invention, a class of reagents is disclosed that can carryout this method. In various embodiments, these reagents can be embeddedin a swipe or other substrate, as a liquid infused via nebulizer, or byother practical means for introduction.

The volatilization reagents described herein offer distinct advantagesover current approaches and offer improved detection of inorganicoxidizers without increasing hardware complexity. The primary challengefor detection of inorganic oxidizers is the low vapor pressure of manyof these materials. Low volatility analytes such as inorganic oxidizersalts (i.e., potassium chlorate) currently require thermal desorption orionization source temperatures on the higher end of, or even exceeding,what is desirable for current detection devices, i.e. temperaturesexceeding 350° C. Achieving such high temperatures is an engineeringchallenge specifically in smaller, field portable systems where size,weight and power must be minimized and long thermal cycling reducessample throughput. Such high temperatures can cause destruction of othermore delicate analytes of interest (such as organic molecules) that maybe coexistent in the analyzed sample. High temperatures can alsoincrease the amount of background signal observed in a detection device,which decreases the quality of quantitative measurements.

The invention discloses reagents offering indirect detection of theanalyte at lower temperatures. Take for example the inorganic oxidizerpotassium perchlorate KClO₄, the detection of which is limited usingconventional atmospheric pressure chemical ionization at temperaturesless than about 350° C. The use of an acidic reagent is disclosed tochemically transform the anion of the oxidizer (e.g. perchlorate, ClO₄⁻) into a much more volatile acid (e.g. perchloric acid, HClO₄). In thiscase, the perchloric acid has a much higher vapor pressure than itsparent oxidizer salt, and is itself easily ionized to create ClO₄ ⁻which is observed in negative ion detection mode. The acidicvolatilizing reagent also supplies an anion (e.g. SO₄ ²⁻) that canassociate with cations of the oxidizing salt (e.g. K⁺), providing chargebalance and thermodynamic stability. The useful result of this concertedchemistry is increased availability of detectable anions (e.g.perchlorate) in the gas phase.

The reagents may be delivered by any reasonable method depending on thephysical state of the reagent(s), as either solid, liquid or vapor. Theintroduction method may be via the solid state on or in a swipe or othersubstrate, liquid infused via nebulizer (inside or outside of aninstrument), or by other practical means for introduction. In each ofthese embodiments, the objective is to broaden the range, type, andperformance of volatilization reagents which in turn allows for the APIdetection of a wider range of threat chemicals with greater signalintensities and better precision at lower temperatures. This advantageis important as the range of threats increases.

In one aspect, the volatilization reagents of this invention arespecific for detection of inorganic oxidizers that will increase theamount of characteristic anions from the analyte entering the gas phasefor subsequent detection. The presence of the volatilization reagent hasthe net effect of increasing the amount of signal detected from ananalyte at a given temperature and allows for improved detection ofthese analytes at lower API source temperatures. Although volatilizationreagents have been disclosed previously for other applications, therehave been no previous disclosures of this acidic volatilization reagentapproach for detection of inorganic oxidizers by API methods.

In another aspect of the invention, acidic volatilization reagents andmethods of use are disclosed for detection of oxidizers. (The terms“volatilization reagent and “evaporative reagent are usedinterchangeably herein.) Through co-introduction of the acidic reagentand the target analyte into the thermal desorption space of aninstrument, the two can communicate with one another resulting in theprotonation of the analyte's anion to form an acid molecule. The overallreaction is generally described as a salt methathesis reaction, wherethe acidic reagent and the analyte salt effectively swap cations andanions with each other. The desired outcome of this reaction is a newacid, containing the anion of the originating analyte salt, where theacid is more volatile and hence easier to detect than the originatingsalt.

Thus, reaction schemes are disclosed in which a proton-containingreagent can react with an ionic analyte by exchanging the analyte'scation with a proton, and the corresponding association of the analyte'sdisplaced cation with the reagent's anion, resulting in increasedvolatility of the analyte's protonated anion which thereby increases itsdetectability in an ion detection apparatus. The proton-containing or“acidic” reagent compound can be a strong acid such as hydrochloric acidor sulfuric acid. Alternatively, the reagent compound can be a weak acidsuch as acetic acid, trifluoroacetic acid, or formic acid. In otherembodiments, the acidic reagent compound can be an acidic salt such asthe alkali-containing acidic salts sodium bisulfate, potassiumbisulfate, or sodium biphosphate. The acidic reagent compound can be inthe solid or liquid phase. The acidity of the reagent, relative to thatof the analyte, can also be tailored to provide reaction selectivitywhen compared to other analytes.

In practice, one or more than one ion can be formed for detection frominteraction between the reagent and analyte(s). Analytes include, butare not limited to ionic components of explosives such as salts ofchlorate, perchlorate, permanganate, dichromate, and osmium tetraoxide.

The methods of the present invention can be practiced where the reactionbetween the chemical (i.e., the acidic reagent) and the analyte occur ona dry, chemically treated collection swipe pre-impregnated with theacidic reagent (i.e. an acidic salt). In some embodiments, in additionto the reagent, an additional thermally labile hydrated salt can beincorporated into the pretreated swipe as an additional source of waterupon heating. In such cases, the solid hydrate can provide an additionalsource of water. In certain embodiments, an aqueous solution of thethermally labile hydrated salt preferably exhibits a pH between about 5and 9. One example of a thermally labile hydrated salt reagent is sodiumthiosulfate pentahydrate. In some embodiments, the swipe can containboth sodium bisulfate as a reagent and sodium thiosulfate pentahydrateas a source of water.

In other embodiments, the reaction between the acidic reagent and theanalyte can occur in the liquid phase after application of a liquidreagent-containing solution to a surface containing the analyte. Forexample, the liquid-phase acidic reagent can be applied directly to aswipe containing the analyte. The liquid-phase acidic reagent can alsobe applied within an ion detection apparatus prior to or during theheating of the analyte containing surface.

In another aspect of the invention, methods are disclosed for detectionof an analyte molecule, X, potentially present in a sample, wherein themethod includes, but is not limited to, treating the sample with anevaporative reagent (e.g., an acidic reagent) to form a higher vaporpressure analog of the analyte if present in the sample, and subjectingthe treated sample to mass spectrometry, whereby the presence of X inthe sample can be deduced. The thus treated sample can then be subjectedto mass spectrometry, e.g. ion mobility spectrometry or the like.

The method can further include associating the evaporative reagent witha swipe prior to sample collection and then using the swipe to obtain asample. In certain embodiments, the reagent can interact with theanalyte (if present in the sample) either prior to desorption in adetection instrument or after it is released into a carrier gas alongwith any target analyte molecules captured by the swipe followingdesorption.

Evaporative reagents according to some embodiments of the invention caninclude at least one acid reagent selected from the group of sulfuricacid, hydrochloric acid, hydrofluoric acid, hydroiodic acid, hydrobromicacid, nitric acid, oxalic acid, water, hydrogen sulfate, phosphoricacid, formic acid, benzoic acid, acetic acid, propionic acid, or otherorganic acids of the form R—COOH where R is an alkyl, substituted alkyl,aryl, or substituted aryl group or at least one other cation donor.

In some embodiments, an acidic evaporative reagent employed for enhanceddetection of an analyte of interest can be a polymeric and/or sulfonicorganic acid. By way of example, the acidic reagent can be a polymericsulfonic acid, such as perfluorinated sulfonic acid. By way of example,the perfluorinated sulfonic acid can be a sulfonated tetrafluoroethylenebased fluoropolymer-copolymer such as Nafion®. Another example of asuitable polymeric organic acid is polystyrene sulfonic acid.

In some embodiments, the acidic evaporative reagent can be a hydratedacidification reagent in solid or liquid phase. By way of example, thehydrated acidification reagent can be a hydrated sulfonate- orsulfate-containing acid, such as sodium bisulfate monohydrate (e.g., insolid phase).

In certain embodiments the evaporative reagent can donate a cation otherthan a proton. For example, the evaporative reagent can include aquaternary ammonium cation donor selected from the group of quaternaryammonium salts that can donate a cation having the formula,N—R1-R2-R3-R4, where R1, R2, R3 and R4 are hydrogen or straight orbranched alkyl, preferably lower alkyl, groups.

In some embodiments, the evaporative reagent can be an acidic salt suchas the alkali-containing acidic salts sodium bisulfate, potassiumbisulfate, or sodium biphosphate. It can also be preferable in someinstances to employ hydrated acidic salts, in which there are one ormore water molecules associated with at least some of the saltmolecules.

In some instances, the methods and reagents of the present invention canbe further enhanced by the addition of water-containing reagents orco-reagents. The presence of water typically increases the effectivenessof the reactions disclosed herein. For example, sodium bisulfate can beemployed as a monohydrate and can essentially supply its own water. Tosupply even more water to assist the reaction, a solid compound (e.g.sodium thiosulfate pentahydrate, Na₂S₂O₃.5H₂O) can be introduced to theswipe material alongside one or more acidic volatilization reagents.

In a related aspect, a swipe for detection of an analyte molecule isdisclosed, which includes a substrate configured to collect a sample foranalysis, and an acidic reagent (e.g., a proton-containing acidicreagent) that is associated with the substrate and is configured toreact with the analyte, if present in the sample, so as to generate ahigher vapor pressure analog of the analyte. The acidic reagent can beassociated with the substrate via a variety of mechanisms, such asphysical entrainment, covalent and/or non-covalent bonds.

The acidic reagent can comprise any of the reagents disclosed above, orothers apparent to those having ordinary skill in the art in view of thepresent teachings. By way of example, in some embodiments, the acidicreagent can be a polymeric and/or sulfonic organic acid, such as apolymeric sulfonic acid (e.g., solid sodium bisulfate monohydrate). Insome embodiments, the acidic reagent can comprise an acidic salt, suchas an alkali-containing acidic salt. Some example of suitablealkali-containing salts include, without limitation, sodium bisulfate,potassium bisulfate, or sodium biphosphate. In some embodiments, theacidic salt further comprises a thermally labile hydrated salt that canprovide an additional source of water upon heating. By way of example,the thermally labile hydrated salt can be sodium thiosulfatepentahydrate.

In a related aspect, a method for detection of an analyte molecule in asample is disclosed, which comprises applying an acidic evaporativereagent in liquid phase to a surface suspected of containing an analyte,whereby generating a higher pressure analog of the analyte is present onthe surface, and thermally desorbing the higher pressure analog foranalysis with mass spectrometry. The acidic reagent reacts with theanalyte in liquid phase after application thereof to the surface togenerate the higher vapor pressure analyte. The liquid-phase acidicreagent can comprise a reagent-containing solution. In some embodiments,the liquid-phase acidic reagent is applied directly to a swipe surfacesuspected of containing the analyte. In some embodiments, theliquid-phase acidic reagent is applied within an ion detection apparatus(e.g., a mass spectrometer, such as an ion mobility spectrometer or adifferential mobility spectrometer) prior to or during the heating ofthe analyte containing surface. The acidity of the reagent relative tothat of the analyte can be tailored to provide reaction selectively whencompared to other analytes. In some embodiments, the acidic evaporativereagent can be a polymeric organic acid and/or a hydrated solid stateacid. Generally speaking, methods for detection of an analyte, X,potentially present in a sample, are disclosed including the steps oftreating the sample with an acidic evaporative reagent having a pKa ofless than 2.5, or less than 2, or less than 0, or less than −2 to form ahigher vapor pressure analog of the analyte if present in the sample,and subjecting the treated sample to mass spectrometry, whereby thepresence of X in the sample can be deduced. The acidic evaporativereagent can be one or more of a polymeric sulfonic organic acid, such asfor example, a polystyrene sulfonic acid or a perfluorinated sulfonicacid, such as for example, a sulfonated tetrafluoroethylene basedfluoropolymer-copolymer. In certain embodiments, the acidic evaporativereagent can be a hydrated acidification reagent or more specifically ahydrated sulfonate- or sulfate-containing acid, such as for example,sodium bisulfate monohydrate.

The methods disclosed herein can be practiced by subjecting the treatedsample to mass spectrometry further comprises subjecting the treatedsample to ion mobility spectrometry or differential mobilityspectrometry. The methods can also be practiced by associating theacidic evaporative reagent with a swipe prior to sample collection andthen using the swipe to obtain a sample. The reagent can interact withthe analyte if present in the sample either prior to desorption in adetection instrument or after it is released into a carrier gas alongwith any target analyte molecules captured by the swipe followingdesorption. The reagent can be a solid or liquid phase reagent appliedto a substrate prior to collection of a sample for analysis.

Alternatively, the reaction between the acidic reagent can occur in theliquid phase after application of a liquid-phase acidic reagent to asurface containing the analyte, for example by applying areagent-containing solution to a swipe which has been used to collect asample or by applying the liquid-phase acidic reagent within an iondetection apparatus prior to or during the heating of the sample. Theacidity of the reagent, relative to that of the analyte, can be tailoredto provide reaction selectivity when compared to other analytes.

The methods disclosed herein can also be practiced by applying aco-reagent capable of releasing water or more specifically a thermallylabile hydrate, such as for example, sodium bisulfate monohydrate. Thus,methods for detection of an analyte molecule, X, potentially present ina sample, are disclosed including the steps of treating the sample withan acidic evaporative reagent and a co-reagent capable of releasingwater to form a higher vapor pressure analog of the analyte if presentin the sample, and subjecting the treated sample to mass spectrometry,whereby the presence of X in the sample can be deduced. The co-reagentcan be a thermally labile hydrate, such as for example, sodium bisulfatemonohydrate, capable of releasing water upon heating. These methods canbe practice together with an acidic reagent is selected from the groupof polymeric organic acids and polymeric sulfonic acids. In the case ofpolymeric sulfonic acids, reagent can include one or more of a polymericsulfonic organic acid, such as for example, a polystyrene sulfonic acidor a perfluorinated sulfonic acid, such as for example, a sulfonatedtetrafluoroethylene based fluoropolymer-copolymer. Alternatively, theacidic evaporative reagent can include a hydrated acidification reagent,or more specifically, a hydrated sulfonate- or sulfate-containing acid,such as for example, solid sodium bisulfate monohydrate. The acidity ofthe reagent, relative to that of the analyte, can be tailored to providereaction selectivity when compared to other analytes. The step ofsubjecting the treated sample to mass spectrometry can further includesubjecting the treated sample to ion mobility spectrometry ordifferential mobility spectrometry.

The acidic reagent and/or the co-reagent can be a solid or liquid phasereagent applied to a substrate, such as a swipe, prior to collection ofa sample for analysis. The reagent can interact with the analyte ifpresent in the sample either prior to desorption in a detectioninstrument or after it is released into a carrier gas along with anytarget analyte molecules captured by the swipe following desorption. Incertain embodiments, the reaction between the acidic reagent and/or thecoreagent can occur in the liquid phase after application of aliquid-phase acidic reagent and/or the co-reagent to a surfacecontaining the analyte, for example by applying a solution containingthe reagent and/or the co-reagent to a swipe which has been used tocollect a sample or by introducing the liquid-phase reagent and/orco-reagent into an ion detection apparatus prior to or during theheating of the sample.

In another aspect, swipes are disclosed for detection of an analytemolecule according to the various methods described herein, For example,the swipe can include a substrate configured to collect or receive asample for analysis, and an acidic evaporative reagent selected from thegroup of polymeric organic acids and polymeric sulfonic acids associatedwith the substrate configured to react with an analyte, if present inthe sample, so as to generate a higher vapor pressure analog of theanalyte.

The swipes can include one or more of a polymeric sulfonic organic acid,such as for example, a polystyrene sulfonic acid or a perfluorinatedsulfonic acid, such as for example, a sulfonated tetrafluoroethylenebased fluoropolymer-copolymer. The swipe can further include a thermallylabile hydrated salt associated with the substrate in solid or liquidform that can provide an additional source of water upon heating. Forexample, the thermally labile hydrate can include sodium thiosulfatepentahydrate.

In yet another aspect, swipes are disclosed for detection of an analytemolecule according to the methods described herein. The swipe caninclude a substrate configured to collect or receive a sample foranalysis, and an acidic reagent and a co-reagent capable of releasingwater associated with the substrate and configured to react with ananalyte, if present in the sample, so as to generate a higher vaporpressure analog of the analyte. The co-reagent can be a thermally labilehydrate, such as for example, sodium bisulfate monohydrate, capable ofreleasing water upon heating. The acidic reagent is selected from thegroup of polymeric organic acids and polymeric sulfonic acids. In thecase of polymeric sulfonic acids, the reagent can include one or more ofa polymeric sulfonic organic acid, such as for example, a polystyrenesulfonic acid or a perfluorinated sulfonic acid, such as for example, asulfonated tetrafluoroethylene based fluoropolymer-copolymer.Alternatively, the acidic evaporative reagent can be a hydratedacidification reagent, or more specifically, a hydrated sulfonate- orsulfate-containing acid, such as for example, solid sodium bisulfatemonohydrate.

In certain embodiments, the acidic reagent and/or co-reagent can beapplied to the swipe prior to, or after, collection of a sample. Theco-reagent can be a thermally labile hydrate, such as for example,sodium bisulfate monohydrate, capable of releasing water upon heating.Alternatively, the acidic reagent is selected from the group ofpolymeric organic acids and polymeric sulfonic acids. The reagent can beone or more of a polymeric sulfonic organic acid, such as for example, apolystyrene sulfonic acid or a perfluorinated sulfonic acid, such as forexample, a sulfonated tetrafluoroethylene based fluoropolymer-copolymer.Alternatively, the acidic evaporative reagent can include a hydratedacidification reagent, or more specifically, a hydrated sulfonate- orsulfate-containing acid, such as for example, solid sodium bisulfatemonohydrate.

In one aspect, an acidic evaporative reagent according to the presentteachings (e.g., an organic polymer acid) can be delivered to an iondetection apparatus, such as, a mass spectrometer, as a liquid infusedvia a nebulizer.

The invention is useful in a wide range of ion detection apparatus, suchas an ion mobility spectrometry, differential mobility spectrometers, ormass spectrometers.

BRIEF DESCRIPTION OF THE DRAWINGS

The appended drawings have been included herein so that theabove-recited features, advantages and objects of the invention willbecome clear and can be understood in detail. These drawings form a partof the specification. It is to be noted, however, that the appendeddrawings should not be considered to limit the scope of the invention.

FIG. 1 is a flow diagram depicting various steps in a method accordingto an embodiment of the present invention for detection of an analytemolecule of interest in a sample,

FIG. 2 illustrates an acidic volatilization reagent scheme according tothe invention for detection of an analyte salt. The acidicvolatilization reagent exchanges its cation (H+) and anion (A−) with theoxidizer analyte salt to create an acid with the same anion as theanalyte salt. The volatility of this acid increases the availability ofthe anion A− for detection in negative ionization mode.

FIG. 3 illustrates representative net reactions according to someembodiments of the invention. Reactions (a) through (f) showvolatilization of chlorate and perchlorate salts using: hydrochloricacid (a, b), sulfuric acid (c, d) and sodium bisulfate (e, f). In eachcase, a more volatile acid, chloric (HClO₃) or perchloric (HClO₄) acidis generated from the relatively involatile analyte salt. Reaction (g)shows how sodium thiosulfate pentahydrate (Na₂S₂O₃.5H₂O) liberates watermolecules in the presence of applied heat (Δq). Water moleculesliberated by reaction (g) help facilitate reactions of type (e) and (f).

FIGS. 4A-4B illustrate the chemical structures of the polymeric acidsNafion® (FIG. 4A) and polystyrene sulfonic acid (FIG. 4B).

FIGS. 5A-5B illustrates a 3D model of anhydrous (5A) and hydrated (5B)sodium bisulfate, respectively.

FIG. 6 schematically illustrates that proton transfer between two solidsis a relatively inefficient process.

FIGS. 7A-7C illustrate the transfer of a proton from a hydrated acidicsalt (sodium bisulfate monohydrate) to solid potassium chlorate viaprotonation of a nearby free and mobile water molecule.

FIG. 8 schematically depicts a swipe according to an embodiment of thepresent invention.

FIG. 9 is a graph of normalized mass spectrometer signal (Y) vs. time(X) obtained by introduction of liquid sulfuric acid (20 μL, 10%) onto a5 μg sample of dried potassium perchlorate in the desorber unit of a TDAPCI mass spectrometer at 150° C.

FIG. 10 is a graph of thermal desorption temperature (Y axis) vs.experimentally measured background subtracted normalized massspectrometer signal (X axis) for detection of chlorate and perchloratesalts (left traces), commonly detected explosive materials (righttraces), and oxidizer salts treated with a dilute acidic reagent (redpoints on the right).

FIG. 11 is a graph of experimentally measured background subtractednormalized mass spectrometer signal (Y axis) vs. pH (X axis) of theacidic volatilization reagent sulfuric acid (H₂SO₄) for detection ofpotassium perchlorate.

FIG. 12 is a graph showing experimentally measured background subtractednormalized mass spectrometer signal (Y axis) for bare potassiumperchlorate at 250° C. and for potassium perchlorate exposed to avariety of different acidic volatilizing reagents at 150° C.

FIGS. 13A-13D are graphs of negative ion TD APCI mass spectra all at athermal desorption temperature of 150° C. FIG. 13A is a graph of theblank background spectrum. FIG. 13B is a graph of 0.5 μg KClO₃(s). FIG.13C is a graph of the background subtracted 150 μg NaHSO₄.H₂O(s). FIG.13D is a graph of the background subtracted of 0.5 μg KClO₃(s) combinedwith 150 μg NaHSO₄.H₂O(s).

FIG. 14 is a graph of the background subtracted mass spectrum (ionintensity v. mass to charge ratio) for enhanced detection of 5 μgpotassium chlorate (KCl0₃) using 73 μg of Nafion™ as an acidificationreagent. The appearance of the ions ClO₃ ⁻, ClO₂ ⁻ and ClO⁻ indicatesthe presence of an inorganic oxidizer salt containing chlorate anions.The thermal desorption temperature was 150° C.

FIG. 15 is a graph of the background subtracted mass spectrum (ionintensity v. mass to charge ratio) for enhanced detection of 0.5 μgpotassium chlorate (KCl0₃) using 900 μg polystyrene sulfonic acid as anacidification reagent. The appearance of the ions ClO₃ ⁻, ClO₂ ⁻ andClO⁻ indicates the presence of an inorganic oxidizer salt containingchlorate anions. The thermal desorption temperature was 150° C.

DETAILED DESCRIPTION

Certain exemplary embodiments will now be described to provide anoverall understanding of the principles of the structure, function,manufacture, and use of the devices and methods disclosed herein. One ormore examples of these embodiments are illustrated in the accompanyingdrawings. Those skilled in the art will understand that the devices andmethods specifically described herein and illustrated in theaccompanying drawings are non-limiting exemplary embodiments and thatthe scope of the present invention is defined solely by the claims. Thefeatures illustrated or described in connection with one exemplaryembodiment can be combined with the features of other embodiments. Suchmodifications and variations are intended to be included within thescope of the present invention.

All publications, patents and patent applications cited herein, whethersupra or infra, are hereby incorporated by reference in their entirety.As used in this specification and the appended claims, the singularforms “a,” “an,” and “the” include plural references unless the contentclearly dictates otherwise. The terms used in this invention adhere tostandard definitions generally accepted by those having ordinary skillin the art. In case any further explanation might be needed, some termshave been further elucidated below.

The term “about,” as used herein, refers to variations in a numericalquantity that can occur, for example, through measuring or handlingprocedures in the real world; through inadvertent error in theseprocedures; through differences in the manufacture, source, or purity ofcompositions or reagents; and the like. Typically, the term “about” asused herein means greater or lesser than the value or range of valuesstated by 1/10 of the stated values, e.g., ±10%. For instance, aconcentration value of about 30% can mean a concentration between 27%and 33%. The term “about” also refers to variations that would berecognized by one skilled in the art as being equivalent so long as suchvariations do not encompass known values practiced by the prior art.Each value or range of values preceded by the term “about” is alsointended to encompass the embodiment of the stated absolute value orrange of values. Whether or not modified by the term “about,”quantitative values recited in the claims include equivalents to therecited values, e.g., variations in the numerical quantity of suchvalues that can occur, but would be recognized to be equivalents by aperson skilled in the art.

The terms “polymeric acids,” “polymeric organic acids,” and polymericsulfonic acids” are used herein consistent with their standard use inthe art. A polymeric acid refers to a polymer having one or acidicfunctional groups. In certain preferred embodiments, the majority, ormore than 75 percent, or all of the repeat units include an acid moietycapable of donating a proton. The repeat units needn't all be identical.The repeating subunits of the polymer can be bonded together to form alinear, a branched or a cyclic structure.

The term “polymeric organic acid” as used herein, is intended toencompass molecules (i) having one or more repeat units that arecovalently linked together, (ii) largely comprising elements that occurin natural materials, namely carbon, hydrogen, oxygen, and nitrogen, and(iii) can donate a proton to another molecule. In some embodiments, thepolymeric organic acids of the invention have at least some carbon atomsin their backbone. In certain preferred embodiments, the majority, ormore than 75 percent, or all of the repeat units include an acid moietycapable of donating a proton. The repeat units needn't all be identical.The repeating subunits of the polymer can be bonded together to form alinear, a branched or a cyclic structure.

The term “polymeric inorganic acid” is typically used to describeanalogs of polymeric organic acids having atomic backbones completelyfree of carbon, such as polysiloxanes (silicon-oxygen backbones),polyphosphates (phosphorous and oxygen backbones), and polysilanes (allsilicon backbones). In some instance, such molecules can have anequivalent effect in inducing evaporation of low volatility analytes. Incertain preferred embodiments, the majority, or more than 75 percent, orall of the repeat units include an acid moiety capable of donating aproton. The repeat units needn't all be identical. The repeatingsubunits of the polymer can be bonded together to form a linear, abranched or a cyclic structure.

The term “polymeric sulfonic acid” as used herein, is intended toencompass molecules (i) having one or more repeat units that arecovalently linked together, (ii) include sulfur and (iii) can donate aproton to another molecule. Similarly to polymeric organic acids, incertain preferred embodiments the majority, or more than 75 percent, orall of the repeat units include an acid moiety capable of donating aproton. Again, the repeat units needn't all be identical and therepeating subunits of the polymer can be bonded together to form alinear, a branched or a cyclic structure.

In some embodiments, the molecular weights of the polymeric organicacids and polymeric sulfonic acids useful herein can range from between1,000 and 1,000,000 Da, or between 10,000 and 200,000 Da, or between50,000 and 150,000 DA. In certain embodiments, a variant of polystyrenesulfonic acid having a molecular weight of about 75,000 Da was useful.However, it is understood to those skilled in the art that in certainaspects of this invention is the polymer's ability to act as an acid,that is to say, to donate a proton. Thus by extension any polymer,independent of its molecular weight, which exhibits such properties, isintended to be encompassed.

In some embodiments, the number of repeat units in the polymeric organicacids and polymeric sulfonic acids useful herein can range from about 50to about 1000 repeat units or between about 100 and about 700 repeatunits or between about 200 and about 600 repeat units. In certainembodiments a variant of polystyrene sulfonic acid having about 400repeat units was useful.

In general, the pKa's of the acidic evaporative reagents (or polymericacids) useful herein are less than 2.5, or less than 2, preferably lessthan 0, or in some instances more preferably less than −2. In someembodiments, sulfonic acids, such as benzene sulfonic acid (pKa=−2.8),polystyrene sulfonic acid (pKa=−3), substituted polystyrene sulfonicacids (pKa=−3 to −6) and Nafion™ a perfluorinated sulfonic acid (pKa=−6)have been useful.

In summary, the key aspects of the acidic evaporative reagents are theirability to convert strong oxidizers (chlorate, perchlorate) into theiracidic form (chloric acid, perchloric acid), while having both nodiscernable vapor pressure and chemical stability to >150° C., thus notoff-gassing any unwanted vapors into the analysis instrument, therebyallowing the analysis instrument to receive only the acidifiedoxidizers.

The term “swipe” is used herein in its general sense to mean a vehiclefor collection of a sample. Typically in the context of IMS, the swipeis a substrate including a least one of paper, fabric, cloth, fibrousmatte, gauze, cellulose, cotton, flax, linen, synthetic fibers andblends of such materials. However, other materials such as ceramic orsemiconductor materials can also be used as “swipes” depending upon theanalysis scheme.

Mass spectrometry is an analytical process for identifying a compound orcompounds in a sample by assessing the molecular weight, chemicalcomposition and structural information based on the mass-to-charge ratioof charged particles. Mass spectrometry is widely considered to have thebest specificity of any technique applicable to a broad class ofexplosive compounds. In general, a sample undergoes ionization to formcharged particles as ions; these charged particles are then passedthrough electric and/or magnetic fields to separate them according totheir mass-to-charge ratio. The terms “mass spectrometry” and“spectrometry” are used herein to encompass techniques that produce aspectrum or spectra of the masses of molecules present in a sample. Massspectrometry includes, but is not limited to, ion mobility spectrometry(IMS), differential mobility spectrometry (DMS), field asymmetric ionmobility spectrometry (FAIMS), and mass spectrometry (MS), all of whichrely upon ionization of the analyte or a complex that includes theanalyte. The analysis performed in spectrometry is typically referred toas “mass/charge” analysis, a method of characterizing the ions detectedby a spectrometer in terms of their mass-to-charge ratio. Theabbreviation m/z is used to denote the quantity formed by dividing themass number of an ion by its charge number. It has long been called themass-to-charge ratio although m is not the ionic mass nor is z amultiple or the elementary (electronic) charge, e. Thus, for example,for the ion C₇H₇ ²⁺, m/z equals 45.5.

The ionization process can be performed by a wide variety of techniques,depending on the phase (solid, liquid, gas) of the sample and theefficiency of the target analyte(s) in question. Some examples of ionsources can include electron ionization, glow discharge ionization,resonant ionization, field desorption, fast atom bombardment,thermospray, desorption/ionization on silicon, atmospheric pressurechemical ionization, spark ionization, inductively coupled plasmaionization, secondary ionization by sputtering ion beams off thetarget's surface, and thermal ionization.

Ambient-pressure ionization, collision-induced ionization, andatmospheric-pressure chemical ionization refer to a characterizationtechniques in which picogram to microgram quantities of an analyte canbe analyzed. The process generally refers to a chemical sample that isintroduced into an ionization region as either a solid, liquid, or gas.In the ionization region, the analyte is in contact with other gases andions that are part of the ionization region. Additional ions areproduced through the collision of the analyte molecules with ions withinthe ionization reagent that are present in the ion source,electro-magnetic device. Inside the ion source, the ionization reagentis present in large excess compared to the analyte. Electrons and/orions entering the source will preferentially ionize the ionizationreagent. Collisions with other ionization reagent molecules will inducefurther ionization, creating positive and/or negative ions of theanalyte. The ions are drawn into the spectrometer by either a carriergas or focused into a beam by an electromagnet, then separated intoindividual beams based on the mass/charge ratio of the ions. The ionbeams are separated in a mass spectrometer and collected eithersequentially in a single detector or simultaneously in a set of multipledetectors to yield isotopic ratios. Highly accurate results require thatsample cross-contamination be minimized.

The traditional methods for explosives detection usually involve wipingthe ambient surface with a special material wipe followed by thermaldesorption/gas phase ionization of the explosive compounds in thepresence of an ionization reagent. The performance of a detectionapproach such as this depends, in part, on the efficiency with which theexplosive compound is transferred from the swipe into the ionizationregion of the analysis instrument during the desorption step. It istherefore desirable to maximize this efficiency for explosive compoundswhich have low vapor pressures.

The terms “desorption,” “desorb” and “desorbing” as used herein refer totechnology of increasing the volatility of molecules, for example targetanalytes, such that they can be removed (separated) from the solid.Thermal desorption is not incineration, but uses heat and a flow ofinert gas to extract volatile and semi-volatile organics retained in asample matrix or on a sorbent bed. The volatilized compounds are theneither collected or thermally destroyed.

In certain embodiments, the reagents of the present invention are lowvolatility compounds. The terms “low volatility” and “low vaporpressure” as used herein are intended to describe compositions that donot readily evaporate or sublimate at room temperature (e.g., at about25° C.). Typically such low volatility compositions are solids orviscous liquids and have a vapor pressure at room temperature of lessthan 1 Torr, or more typically less that 10⁻¹ Torr. In some preferredembodiments, the low volatility reagents of the present invention canhave a vapor pressure at room temperature of or less that 10⁻² Torr or,more preferably, less that 10⁻³ Torr.

With reference to flow chart of FIG. 1, in some embodiments, a methodfor detection of an analyte molecule potentially present in a sample,e.g., inorganic oxidizers such as chlorates and perchlorates, isdisclosed that includes treating the sample with an evaporative reagentto form a higher vapor pressure analog of the analyte if present in thesample (step 1). The treated sample can then be subjected to massspectroscopy to detect the analyte, if present in the sample (step 2).The evaporative reagent can be an acidic volatilization reagent. Forexample, in some embodiments, the acidic volatilization reagent can be apolymeric organic acid, such, a polymeric sulfonic acid. In someembodiments, the acidic volatilization reagent can be a hydrated solidstate acidification reagent, such as, potassium bisulfate monohydrate.

FIG. 2 provides a reagent scheme for detection of an oxidizer inaccordance with the present teachings, where an acidic volatilizationreagent induces a salt metathesis reaction to increase the availabilityof an originating salt's anion for detection in a negative ionizationmode. The increased vapor pressure of the newly formed acid results insignificantly increased detection sensitivity and the ability to performthe detection at lower temperatures. Compounds that can act as acidicvolatilization reagents for such enhanced detection include, withoutlimitation, strong acids, weak acids, and acidic salts. An acidic saltcan dissociate to release a weak acid via thermal decomposition, or bydissociative solvation in the presence of water. The weak acid releasedfrom the acidic salt can then participate in the salt methathesisreaction shown in FIG. 2.

In some instances, the use of a liquid reagent may not be preferable.Additionally, the use of a strong acid (even one that is substantiallydiluted) may not be desirable or allowed in certain environments. Insuch instances, the use of solid acidic salts (e.g. sodium bisulfate,NaHSO₄) can be the preferred method of providing an acidic reagent.These solids may be applied to existing swipes or introduced duringmanufacturing of chemically treated swipes. The hydrated form of sodiumbisulfate easily vaporizes at low temperatures, liberating the weak acidHSO₄ ⁻ which is effective at participating in salt metathesis reactions.The presence of water typically increases the effectiveness of suchreactions, and that too can be thermally released from a solid salt.Sodium bisulfate can exist as a monohydrate and can essentially supplyits own water. To supply even more water to assist the reaction, a solidcompound (e.g. sodium thiosulfate pentahydrate, Na₂S₂O₃.5H₂O) can beintroduced to the swipe material alongside the acidic volatilizationreagent. Numerous such hydrates exist, and when choosing one, threecharacteristics should be considered. First, the salt of the hydrateshould not interfere with the desired salt methathesis reaction. Morespecifically, it should not compete with the analyte for protons.Secondly, the hydrate should melt and release its hydrated watermolecules at temperatures easily attainable in a thermal desorber (i.e.,<200° C. or more preferably <150° C.). Lastly, the hydrate shouldcontain as many associated water molecules as possible for the sake ofefficiently.

FIG. 3 outlines reactions that are representative of some embodiments ofthe present invention. More specifically, reactions (a) through (f) showvolatilization of chlorate and perchlorate salts using: hydrochloricacid (a, b), sulfuric acid (c, d) and sodium bisulfate (e, f). In eachcase, a more volatile acid, chloric (HClO₃) or perchloric (HClO₄) acidis generated from the relatively involatile analyte salt. Reaction (g)shows how sodium thiosulfate pentahydrate (Na₂S₂O₃.5H₂O) liberates watermolecules in the presence of applied heat (Δq). Water moleculesliberated by reaction (g) help facilitate reactions of type (e) and (f).

The term “hydrate” as used herein is intended to encompass compositionsin which there are one or more water molecules associated with at leastsome of the reagent or co-reagent molecules.

A series of acidic (or other) reagents may be utilized by introductionsimultaneously or at discrete times and temperatures to induce selectivereactions with expected oxidizers (e.g. reagent A for perchlorate,reagent B for chlorate, reagent C for hydrogen peroxide, reagent D forTATP, reagent E for HMTD). This invention will allow introduction ofmultiple reagents, if required for more selective detection.

In some embodiments, polymeric organic acids are employed as evaporativereagents for enhanced detection of an analyte molecule present in asample, for example, for enhanced detection of inorganic oxidizers, suchas chlorates and perchlorates. In some embodiments, the polymericorganic acid can have a molecular weight, for example, in a rangebetween 1,000 and 1,000,000 Da, or between 10,000 and 200,000 Da, orbetween 50,000 and 150,000 DA. Further, in some embodiments, the numberof repeating units of the backbone of the polymeric organic acid canrange from about 50 to about 1000 repeat units or between about 100 andabout 700 repeat units or between about 200 and about 600 repeat units.

Some examples of suitable acidic evaporative reagents include, withoutlimitation, perfluorinated sulfonic acids (e.g., such as but not limitedto Nafion™) and polymeric sulfonic acids (e.g., such as but not limitedto polystyrene sulfonic acid).

Without being bound to any particular theory, polymeric organic acids,such as perfluorinated sulfonic acids, can act as effective evaporativeagents in accordance with some embodiments of the present teachingsbecause (1) their sulfonic functional groups render them extremelyacidic, e.g., a pKa of less than 2.5, or less than 2, preferably lessthan 0, or in some instances more preferably less than −2. (2) thesepolymeric acids are known to be highly hygroscopic, and typically havewater molecules absorbed on their surface that can aid in protontransfer, and (3) these polymeric organic acids can be tailored torelease their protons without contributing other materials to the gasphase. As such, in some embodiments, the polymeric organic acids areselected that can enhance the detection of analyte molecules of interestin a very “clean” fashion, i.e., without generating unwanted byproducts.By way of example, this feature can be valuable for explosive tracedetection (ETD) as many ETD equipment can manifest strong spectralsignals from even small contributions of nuisance chemical byproducts tothe gas phase.

In some embodiments, the polymeric organic acids are employed in a solidphase while in other embodiments the polymeric organic acids areemployed in liquid phase for enhanced detection of an analyst in asample.

As discussed above, the intended goal of using acidification reagentsfor enhanced detection is to efficiently convert inorganic oxidizersalts into their detectable volatile analogs. In some cases, oneunintended consequence of this reagent chemistry can be desorption ofthe acidification reagent itself (or byproducts thereof) during thethermal desorption process in an ETD. This phenomenon has been observedwith sodium bisulfate in both the solid and solution state (See, e.g.,FIG. 13C). The appearance of new peaks in the IMS or MS is undesirable,as any new peak adds to the ‘spectral clutter’ and could potentially beconfused for threat compounds in some circumstances.

An idealized acidification reagent would convert the anions of inorganicoxidizer salts into their high vapor pressure acidic analogs and make noother contribution to the detectable ensemble of molecules in the gasphase. This could be accomplished by using an acid in which the counteranion (negatively charged component that remains after donating aproton) has a sufficiently low vapor pressure at the thermal desorptiontemperature. Another strategy involves tethering the counter anion tothe substrate of the ETD swipe used for sample gathering.

One advantage polymeric acids according to the present teachings is thatthe use of such polymeric acids can allow effectively employing both ofthe above strategies to minimize, and preferably inhibit, contributionto observed spectral clutter. As discussed in more detail below,Applicants have demonstrated the ability of these materials to ‘turn on’the acidic enhancement mechanism with little to no contribution toobserved spectral clutter.

By way of example, FIGS. 4A and 4B show the structures of two polymericsulfonic acids, namely Nafion™ and polystyrene sulfonic acid, that aresuitable for enhanced detection of analytes of interest, andparticularly chlorates and perchlorates in accordance with the presentteachings. These acids have polymeric backbones that can have arbitrarylengths, from a few subunits to a bulk polymer. Each polymer can havenumerous acidic groups branching from the side. While in someembodiments sulfonic acids are used, in other embodiments other acidicfunctional groups could be utilized. One advantage of these acids isthat the sulfonic acid group, which remains behind after the proton (H⁺)has left the acidic group, is covalently attached to the relativelymassive and nonvolatile polymer backbone. This inhibits the ability ofthe counter anion to enter the gas phase and introduce unwanted spectralclutter.

As discussed above, in some embodiments, solid-state acidificationreagents can be used for enhanced detection of analytes of interest. Insome such embodiments, the presence of microscopic amounts of freeexcess water (such as water released from a hydrated crystal uponthermal desorption) can catalyze proton transfer from the acidic reagentto the analyte molecule of interest. Without being bound to anyparticular theory, the water in hydrate compounds can retain its intactmolecular identity. While such water molecules participate in theformation of a crystal lattice, they can be reversibly added orliberated from the crystal under proper conditions.

By way of example, the presence of hydrated or absorbed water on/in asolid-state acidification reagent can help facilitate the protontransfer mechanism between an acidic reagent and a target chlorate orperchlorate salt. Both inorganic and organic solid state acids can existas hydrates. One such example of an inorganic acid that can exist as ahydrate is sodium bisulfate, shown in FIGS. 5A and 5B, in its anhydrousand hydrated states, respectively.

Chemistry in liquid and gas phase, which are inherently mobile phases ofmatter, typically proceeds more efficiently than solid-state chemistry.For example, as shown schematically in FIG. 6, a solid-state transfer ofa proton between the bisulfate anion of anhydrous sodium bisulfate andthe chlorate anion of potassium chlorate (a two-body reaction mechanism)can be a relatively inefficient process.

The presence of water greatly enhances the efficiency of protontransfer, because water molecules are highly mobile themselves (ineither the liquid or gas phases), and individual water molecules areable to accept extra protons. The protonated water molecules arereferred to as hydronium ions. Hydronium ions on their own are quitemobile, and can also rapidly transfer their ‘extra’ proton toneighboring water molecules.

A solid hydrate (such as sodium bisulfate) can shed water molecules whenheated. Thus, in a typical thermal desorption environment, like thosefound in commercial IMS based ETD equipment, heated hydrates andhygroscopic acids can be surrounded by copious amounts of ‘free’ watermolecules. These free water molecules are in a good position to getprotonated by an acidifying reagent and efficiently transfer that protonto a solid potassium chlorate surface some distance away.

By way of example, FIGS. 7A-7C schematically show how a single watermolecule can promote the transfer of the proton between the two solids.While these figures show a single water molecule assisting the protontransfer mechanism, more water molecules (released from other hydratedcrystals or from the ambient environment) could also participate in theproton transfer. In these situations, the newly formed hydronium cationwould simply transfer its ‘extra’ proton to a neighboring water moleculein the direction of the potassium chlorate. Water vapor or liquid is aneffective conductor of protons, and acts to catalyze the proton transferreaction.

More specifically, FIG. 7A depicts that the sodium bisulfate transfers aproton from a hydronium cation to a nearby water molecule. The hydroniumion is highly mobile and can readily move between the two solid surfacesto react with the chlorate anion of potassium chlorate, as shown in FIG.7B. FIG. 7C shows that the hydronium cation donates a proton to thechlorate anion to form chloric acid. The generated chloric acid ishighly volatile and hence can be easily detected.

In some embodiments, swipes for use in detection of analytes ofinterest, such as, chlorates and perchlorates, are disclosed, which areimpregnated with one or more evaporative reagents according to thepresent teachings. By way of example, FIG. 8 schematically depicts aswipe 10 (also referred to as smear, wipe) according to one embodiment,which includes a substrate 12. The substrate 12 can be formed of avariety of different materials, such as paper, fabric, cloth, fibers,glass, or synthetic material. By of example, in some embodiments, thesubstrate is fabricated of polyester, muslin, or cotton. The substratecan be preferably formed of a material that can be resistant to chemicaldegradation during testing in the approximate pH range of 0.1 through 14to avoid reacting or decomposing. Further information regarding suitablesubstrates can be found in published U.S. patent application havingpublication no. 2014/0030816 entitled “Reagent Impregnated Swipe ForChemical Detection,” which is herein incorporated by reference in itsentirety.

One or more evaporative reagents 14 according to the present teachings,such as those disclosed herein (e.g., polymeric sulfonic acids) isdeposited on, embedded in, or otherwise associated with, the substrate10. The reagents 14 can be associated with the substrate via a varietyof different physical and/or chemical mechanisms, such as physicalentrainment, non-covalent and/or covalent bonds. In some embodiments,one or more polymeric organic acids can be associated with the substrateby tethering the polymer backbone to the substrate, e.g. via covalentbonds. In some such embodiments, one or more linkers may be employed totether the polymeric acid to the substrate.

In some embodiments, the swipe 10 can be heat resistant, absorbentand/or chemically resistant at elevated temperatures and can havehydrophilic properties for wetting when using fluid reagents. While insome embodiments, the swipe has a sheet-like structure, in otherembodiments, it can have a three-dimensional structure.

Commercial applications include use in all industries involved inchemical detection including but not limited to explosives detection,chemical warfare detection, homeland security, and toxic industrialchemical and pollution monitoring.

EXAMPLES

This invention has been reduced to practice for detection of potassiumperchlorate, sodium perchlorate, potassium chlorate, and sodium chloratevia API mass spectrometry. As described earlier, in negative-ion-modeatmospheric pressure chemical ionization, the vaporization (and henceionization) efficiency of ‘bare’ oxidizer salts is extremely limited.The examples provided below are only for illustrative purposes, and arenot intended to necessarily illustrate the optimal ways of practicingthe invention and/or optimal results that may be obtained.

Example 1

FIG. 9 illustrates enhancement in observed mass spectrometer ion signalupon addition of an acidic volatizing reagent to an inorganic oxidizersalt. More specifically, FIG. 9 is a graph of normalized massspectrometer signal (Y) vs. time (X) obtained by introduction of liquidsulfuric acid (20 μL, 10%) onto a 5 μg sample of dried potassiumperchlorate in the desorber unit of a TD APCI mass spectrometer at 150°C. In this instance, the mass spectrometer was in MRM mode, measuringthe 99→83 Da loss channel. Note the dramatic increase in signal at 0.14minutes when the acidic volatilizing reagent was pre-mixed with thepotassium perchlorate sample. In the absence of the acidic volatilizingreagent, no signal was observed from potassium perchlorate at such a lowtemperature.

Example 2

In another example, in order to increase the amount of free perchlorateanion available for detection, an acidic reagent known to protonate theperchlorate anion (³⁵ClO₄ ⁻) was added to a dried potassium perchloratesample. In these experiments, a liquid reagent, namely 5 μL of 0.01%sulfuric acid (CAS#7664-93-9), was added over a previously dried 5-μgsample of potassium perchlorate on an inert silicon wafer surface. Thesilicon wafer was then transferred to a thermal desorption unit on a TDAPCI source for detection via mass spectrometry. The experimental datapresented in FIG. 10 shows the benefits of acidic reagents in terms ofboth increased mass spectrometer signal and enabling thermal desorptionto take place at lower temperatures.

More specifically, FIG. 10 is a graph of thermal desorption temperature(Y axis) vs. experimentally measured background subtracted normalizedmass spectrometer signal (X axis) for detection of chlorate andperchlorate salts (left traces), commonly detected explosive materials(right traces), and oxidizer salts treated with a dilute acidic reagent(red points on the right). Increased detection sensitivity is denoted bylarger values on the X axis. This figure demonstrates how the presenceof an acidic volatilization reagent increases the signal level. Thediagonal red arrow in the center of the figure illustrates a 10⁴ factorincrease in observed mass spectrometer signal at decreased thermaldesorption temperature as a result of treating chlorate and perchloratesalts with dilute sulfuric acid. As shown in FIG. 10, the net result ofusing the acidic volatilization reagent is increased sensitivity (on theorder of a factor of 10⁴ for the dilute sulfuric acid solution used) ata modest thermal desorption temperature of 150° C. It is important tonote that this thermal desorption temperature is also near the optimalvalue for the other more conventionally detected explosives (TATP, PETN,and RDX) included in FIG. 10. This demonstrates that the acidicvolatilization reagents can operate in a temperature regime that favorscurrent detection methods and instrumentation.

Example 3

In order to determine the minimum acidity (maximum pH) at which theacidic volatilization mechanism was still functional, a series of signalvs. pH measurements were carried out. FIG. 11 shows the results of anexperiment conducted in order to determine the maximum acceptable pH forthe acidic volatilization reagent sulfuric acid (H₂SO₄). FIG. 11 is agraph of experimentally measured background subtracted normalized massspectrometer signal (Y axis) vs. pH (X axis) of the acidicvolatilization reagent sulfuric acid (H₂SO₄) for detection of potassiumperchlorate. The numbers next to the data points indicate the percentsolution (v/v) of sulfuric acid corresponding to each measurement. A0.01% (pH 2.74) sulfuric acid solution still produces an acceptableamount of signal enhancement for detection of the perchlorate anion. Asshown in FIG. 11, the ion signal generated by acid volatilization ofpotassium perchlorate (KClO₄) begins to drop off after a pH of 2 isreached. An acceptable result (in terms of enhancement of the normalizedsignal compared to bare potassium perchlorate) is still achieved at a pHof 2.74, which is equivalent to a 0.01% sulfuric acid solution.

Example 4

FIG. 12 presents an overview comparing background subtracted normalizedmass spectrometer signal for bare potassium perchlorate solid in a TDAPCI source and potassium perchlorate treated with a variety of acidicvolatilizing reagents. In FIG. 12, experimentally measured backgroundsubtracted normalized mass spectrometer signal (Y axis) is shown forbare potassium perchlorate at 250° C. and for potassium perchlorateexposed to a variety of different acidic volatilizing reagents at 150°C. All of the acidic volatilizing agents were presented to the solidpotassium perchlorate in liquid form in noted concentrations (v/v)except for the sodium bisulfate data point denoted as solid (s).

Example 5

FIGS. 13A-13D show mass spectra of sodium bisulfate monohydrateenhancing the detection of potassium chlorate. It is clear that theblank background spectrum (FIG. 13A.) and the spectrum of potassiumchlorate by itself (FIG. 13B) are markedly similar. Sodium bisulfatemonohydrate produces a spectrum of its own (FIG. C). The combination ofpotassium chlorate and sodium bisulfate monohydrate produces new andunique signals that indicate the presence of chlorate anions (ClO₃ ⁻,m/z=83, 85) as well as chlorate breakdown products (chlorite, ClO₂ ⁻, atm/z=67, 69 and hypochlorite, ClO⁻, at m/z=51, 53).

Example 6

It was observed that polymeric acids can be highly effective atenhancing trace detection of inorganic salts with a thermal desorptionatmospheric pressure chemical ionization (TD APCI) mass spectrometer.More specifically, both Nafion™ and polystyrene sulfonic acid wereobserved to enhance detection of chlorates and perchlorates from themilligram/microgram detectable range down to the microgram/nanogramdetectable range, an increase in detection on the order of three ordersof magnitude.

FIGS. 14 and 15 present representative mass spectra showing detection ofpotassium chlorate (KClO₃) with both Nafion™ and polystyrene sulfonicacid, respectively. It is clear that these polymeric acids are strongenough to enable the acidification/volatilization, and their hygroscopicproperty ensures that they carry enough absorbed water to enable thereaction to proceed in an efficient manner. The relative lack of clutterin these mass spectra indicates that these polymeric acids are enablingthe acidification/volatilization mechanism without introducing unwantedby-products to the gas phase ion population.

One skilled in the art will appreciate further features and advantagesof the invention based on the above-described embodiments. Accordingly,the invention is not to be limited by what has been particularly shownand described, except as indicated by the appended claims. All patents,publications and references cited herein (including the following listedreferences) are expressly incorporated herein by reference in theirentirety.

The invention claimed is:
 1. A method for detection of an analytemolecule, X, present in a sample, the method comprising: treating thesample with an acidic evaporative reagent to form a higher vaporpressure analog of the analyte molecule, X, and subjecting the treatedsample to mass spectrometry, whereby the presence of analyte molecule,X, in the sample can be deduced, wherein said acidic evaporative reagentcomprises a polymeric sulfonic acid.
 2. The method of claim 1, whereinsaid polymeric sulfonic acid comprises any of a perfluorinated sulfonicacid and a polystyrene sulfonic acid.
 3. The method of claim 2, whereinsaid perfluorinated sulfonic acid comprises a sulfonatedtetrafluoroethylene based fluoropolymer-copolymer.
 4. The method ofclaim 1, wherein the method further comprises associating the acidicevaporative reagent with a swipe prior to sample collection and thenusing the swipe to obtain the sample.
 5. A method for detection of ananalyte molecule, X, present in a sample, the method comprising:treating the sample with an acidic evaporative reagent by incorporatingthe acidic evaporative reagent into a swipe to interact with the analytemolecule, X, present on the swipe wherein the reagent interacts with theanalyte molecule, X, after it is released into a carrier gas along withthe analyte molecule, X, captured by the swipe following thermaldesorption.
 6. A method for detection of an analyte molecule, X, presentin a sample, the method comprising: treating the sample with an acidicevaporative reagent to form a higher vapor pressure analog of theanalyte molecule, X, subjecting the treated sample to mass spectrometry,whereby the presence of the analyte molecule, X, in the sample can bededuced, and applying a coreagent that releases water.
 7. The method ofclaim 6 wherein the co-reagent is a thermally labile hydrate.